The present invention relates generally to polymers and more specifically to polymers having useful optical and chemical resistance properties.
With the wealth of genetic information available from genome projects, focus has centered on the analysis of arrays of genes and proteins. Experimentally, this analysis is made possible with the development of microarray technologies where thousands or tens-of-thousands of genes are surveyed with a single biochip. Leading biochip technologies are the DNA-based chips, with protein chips being developed only recently.
Biochips have been constructed using both deposition techniques and by synthesis of the biopolymer (DNA or peptide) directly on the solid support. Both glass and nylon membranes have been used as solid supports for DNA-based chips (Lockhart and Winzeler Nature, 405:827-836 (2000)). Of these, glass allows greater density arrays and more flexibility for detection. In particular, fluorescence techniques have been used to interrogate DNA arrays. DNA-based biochips are constructed using either deposition of DNA onto aminosilane or poly-lysine coated slides or by direct synthesis of the DNA on derivatized glass using light-directed synthesis (Sundberg and Fujimoto, U.S. Pat. No. 5,624,711 (1997)).
Noncovalent depostion of the DNA on the chip allows the flexibility to generate custom biochips. However, the random orientation of the DNA on the surface can reduce sensitivity, and the absence of covalent attachment prevents the reuse of the chips. Covalent attachment of DNA to glass slides and silicon wafer was made possible by methods developed at Affymetrix (Pirrung et al., U.S. Pat. No. 5,143,854 (1992)). Glass slides modified with silicon derivatives are used as a support for light-directed synthesis using projection masks similar to those used in the photolithographic etching of computer chips. For the synthesis of a single 20-mer chip, eighty different masks are necessary. The high cost for producing each mask makes this method most suitable for the production of multiple copies of the same oligonucleotide array. Additionally, many of these solid supports have performance problems including pH instability, poor physical strength, solvent incompatability, chemical reactivity, and nonspecific absorption of biomolecules. As the result of instability to reagents used in chemical regeneration, biochips synthesized on these supports are not reusable. As an alternative to glass and silicon supports, polypropylene has been proposed (Matson et al., Anal. Biochem. 217: 306-310 (1994)). While polypropylene provides many advantages over glass in terms of chemical and solvent stability and physical strength, the poor optical properties and flexibility of the plastic make polypropylene unsuitable for most array applications.
The development of biochips has followed a trend of miniaturization in the biotechnology and pharmaceutical industries whereby reagent costs and analysis speeds are minimized through the reduction of assay volumes. This miniaturization is especially apparent in high throughput screening where 96-well, 384-well, and 1536-well plates with assay volumes of 400 μL to 1 μL, respectively, are in routine use. The microwell plates are conventionally made from clear, white, or black plastic, such as polypropylene, polystyrene, or acrylonitrile-butadiene-styrene (ABS) that has relatively low intrinsic fluorescent properties. The use of microwell plates also permits very dense storage of collectives of discrete compounds for later testing as films in addressable grid positions, thus reducing the number of handling steps for the analysis of a collection of compounds.
Microwell plates have also been used in combinatorial chemistry where organic and inorganic compounds are synthesized directly in the microwells in solution, on beads, or on the microwell surface itself. As a result of the many solvents and reagents used in combinatorial chemistry, these microwell plates have essentially been limited to polypropylene. Polypropylene, an opaque thermoplastic, has poor hardness and flexibility characteristics that lead to deformation and inaccuracies in the final molded product. Consequently, it would be desirable to provide a polymeric support material that is transparent, shows low fluorescence, and is resistant to organic solvents that can be used for the construction of biochips, microwell plates and other solid supports that allow increased throughput screening by incorporating a large number of small wells.
Thus, there exists a need for a solid support having optical properties and chemical stability suitable for chemical synthesis. The present invention satisfies this need, and provides related advantages as well.